11-47410213-G-T

Position:

• chr11-47410213-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128225.3(SLC39A13):​c.119G>T​(p.Arg40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC39A13 NM_001128225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

SLC39A13 (HGNC:20859): (solute carrier family 39 member 13) This gene encodes a member of the LIV-1 subfamily of the ZIP transporter family. The encoded transmembrane protein functions as a zinc transporter. Mutations in this gene have been associated with the spondylocheiro dysplastic form of Ehlers-Danlos syndrome. Alternate transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

SLC39A13 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1426236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A13	NM_001128225.3	c.119G>T	p.Arg40Leu	missense_variant	2/10	ENST00000362021.9	NP_001121697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A13	ENST00000362021.9	c.119G>T	p.Arg40Leu	missense_variant	2/10	1	NM_001128225.3	ENSP00000354689.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461126 Hom.: 0 Cov.: 73 AF XY: 0.00000138 AC XY: 1 AN XY: 726896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.014	T;T;.;T;T;.;.;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;.;.;.;N;N;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.73	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.29	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;T;T;T;T
Polyphen		0.0020, 0.0010, 0.0070	.;.;.;.;B;B;.;.;B
Vest4		0.17
MutPred		0.54		Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);Loss of methylation at R40 (P = 0.0327);
MVP		0.58
MPC		0.42
ClinPred		0.083	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.054
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35741412; hg19: chr11-47431764;